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1,3-BUTADIENE
This substance was considered by previous Working Groups in June
1985 (IARC, 1986; see also correction, IARC, 1987a), March 1987
(IARC, 1987b), October 1991 (IARC, 1992) and February 1998 (IARC,
1999). Since that time, new data have become available, and these
have been incorporated into the monograph and taken into
con-sideration in the present evaluation.
One of the metabolites of 1,3-butadiene, 1,2:3,4-diepoxybutane,
was also evaluated previously by an IARC Working Group (IARC,
1976), and its re-evaluation by the present Working Group is
included in this monograph.
1. Exposure Data
1.1 Chemical and physical data
Butadiene
1.1.1 Nomenclature (IARC, 1999; IPCS-CEC, 2000; O’Neil,
2006)
Chem. Abstr. Serv. Reg. No.: 106-99-0 Chem. Abstr. Name:
1,3-Butadiene IUPAC Systematic Name: 1,3-Butadiene RTECS No.:
EI9275000 UN TDG No.: 1010 (stabilized) EC No.: 601-013-00-X
Synonyms: Biethylene; bivinyl; butadiene; buta-1,3-diene;
α,γ-butadiene; trans-butadiene; divinyl; erythrene; pyrrolylene;
vinylethylene
1.1.2 Structural and molecular formulae and relative molecular
mass
H2C CH2CHCH C4H6 Relative molecular mass: 54.09
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46 IARC MONOGRAPHS VOLUME 97
1.1.3 Chemical and physical properties of the pure substance
From IARC (1999), IPCS-CEC (2000), Lide (2005) and O’Neil (2006)
unless otherwise specified (a) Description: Colourless gas (b)
Boiling-point: –4.4 °C (c) Melting-point: –108.9 °C (d) Density:
d24
0 0.6149 (e) Spectroscopy data: Ultraviolet (Grasselli &
Ritchey, 1975), infrared (Sadtler
Research Laboratories, 1995; prism [893a], grating [36758]),
nuclear magnetic resonance and mass spectral data (NIH/EPA Chemical
Information System, 1983) have been reported.
(f) Solubility: Slightly soluble in water (1 g/L at 20 °C);
soluble in ethanol, diethyl ether, benzene and organic solvents;
very soluble in acetone (see also Verschueren, 1996)
(g) Vapour pressure: 120 kPa at 0 °C; 273 kPa at 25 °C (Grub
& Löser, 2005) (h) Relative vapour density (air = 1): 1.87
(Verschueren, 1996) (i) Stability: As a result of flow and
agitation, electrostatic charges can be gen-
erated. The vapours are uninhibited and may form polymers in
vents or flame arresters of storage tanks, and result in the
blockage of vents. On exposure to air, the substance can form
peroxides and initiate explosive polymerization. It may also
polymerize due to warming by fire or an explosion. It decomposes
explosively on rapid heating under pressure and may react
vigorously with oxidants and many other substances, causing fire
and explosion hazards (IPCS-CEC, 2000).
(j) Flash-point: –76 °C (IPCS-CEC, 2000) (k) Auto-ignition
temperature: 414 °C (IPCS-CEC, 2000) (l) Explosive limits: Lower,
1.1%; upper, 12.3% (IPCS-CEC, 2000) (m) Octanol/water partition
coefficient: log Pow, 1.99 (IPCS-CEC, 2000) (n) Odour threshold:
1–1.6 ppm [2.2–3.5 mg/m3] (recognition) (ACGIH, 2001) (o) Henry’s
law constant (calculated at 25 °C and 101.325 kPa): 7460 Pa ×
m3/mol (Health Canada, 1999) (p) Organic carbon partition
coefficient: log Koc, 1.86–2.36 (Health Canada, 1999) (q)
Conversion factor: mg/m3 = 2.21 × ppm1
Diepoxybutane
Diepoxybutane is the racemic mixture of four different isomers,
with the following Chem. Abstr. Serv. Reg. Nos: 1464-53-5,
diepoxybutane; 298-18-0, (±)-diepoxybutane;
1 Calculated from: mg/m3 = (molecular weight/24.47) × ppm,
assuming normal temperature (25 °C) and pressure (101.3 kPa)
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1,3-BUTADIENE 47
564-00-1, meso-diepoxybutane; 30419-67-1, D-diepoxybutane;
30031-64-2, L-diepoxy-butane.
1.1.1 Nomenclature
Chem. Abstr. Name: 2,2′-Bioxirane IUPAC Systematic Name:
1,2:3,4-Diepoxybutane Synonyms: Butadiene dioxide (diepoxybutane);
1,3-butadiene diepoxide ((±)-di-epoxybutane);
D-1,2:3,4-diepoxybutane (D-diepoxybutane): L-1,2:3,4-diepoxybutane;
(5,5)-1,2:3,4-diepoxybutane (L-diepoxybutane)
1.1.2 Structural and molecular formulae and relative molecular
mass
O
C
H
H2C CH2
H
C
O C4H6O2 Relative molecular mass: 86.10
1.1.3 Chemical and physical properties
From O’Neil (2006) (a) Description: Colourless liquid (b)
Boiling-point: 138 °C (c) Melting-point: –19 °C (d) Solubility:
Miscible with water (hydrolyses) (e) Vapour pressure: 918 Pa at 25
°C
1.1.4 Technical products and impurities
In the production of polymers such as styrene–butadiene
copolymer resins, the polymerization catalysts used are sensitive
to some impurities such as oxygen and moisture. Butadiene that is
used for polymerization is 99.9% pure. Up to 22 different volatile
components of light molecular mass were detected as impurities with
the ASTM method D2593-93 (reapproved in 2004; ASTM, 2004).
1.1.5 Analysis
Selected methods for the analysis of butadiene in various
matrices are listed in Table 1. Those for the analysis of butadiene
in air have been evaluated; there appears to be no single preferred
method, but more recent ones give a higher performance. Thermal
desorption provides high levels of accuracy and precision (Bianchi
et al., 1997).
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48 IARC MONOGRAPHS VOLUME 97
Several gas detector tubes are used in conjunction with common
colorimetric reactions to detect butadiene. The reactions include
the reduction of chromate or di-chromate to chromous ion and the
reduction of ammonium molybdate and palladium sulfate to molybdenum
blue (Saltzman & Harman, 1989).
Passive dosimeters that use different techniques (thermal
desorption and gas chromatography, colorimetric reactions) are also
available for the detection of butadiene.
Table 1. Selected methods for the analysis of butadiene in
various matrices
Sample matrix Sample preparation Assay procedure
Limit of detection
Reference
Air Adsorb (charcoal); extract (carbon disulfide)
GC/FID 200 µg/m3 Occupational Safety and Health Administration
(1990a)
Adsorb (charcoal); extract (dichloromethane)
GC/FID 0.2 µg/sample Eller (1994)
Adsorb on Perkin-Elmer ATD 400 packed with polymeric or
synthetic adsorbent material; thermal desorption
GC/FID 200 µg/m3 Health and Safety Executive (1992)
3M passive monitoring GC/FID 0.029 mg/m3
for a 20.5-L sample
Anttinen-Klemetti et al. (2004)
Foods and plastic food-packaging material
Dissolve (N,N-dimethylacetamide) or melt; inject headspace
sample
GC/MS–SIM ~1 µg/kg Startin & Gilbert (1984)
Plastics, liquid foods
Dissolve in ortho-dichlorobenzene; inject headspace sample
GC/FID 2–20 µg/kg Food and Drug Administration (1987)
Solid foods Cut or mash; inject headspace sample
GC/FID 2–20 µg/kg Food and Drug Administration (1987)
GC/FID, gas chromatography/flame ionization detection;
GC/MS–SIM, gas chromatography/mass spectrometry with single-ion
monitoring
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1,3-BUTADIENE 49
1.2 Production and use
1.2.1 Production
Butadiene was first produced in the late nineteenth century by
pyrolysis of various organic materials. Commercial production began
in the 1930s (Sun & Wristers, 2002).
(a) Manufacturing processes
(i) Ethylene co-production
Butadiene is manufactured primarily as a co-product of the steam
cracking of hydro-carbon streams to produce ethylene. This process
accounts for over 95% of global buta-diene production (White,
2007).
Steam cracking is a complex, highly endothermic pyrolysis
reaction, during which a hydrocarbon feedstock is heated to
approximately 800 °C and 34 kPa for less than 1 sec and the
carbon–carbon and carbon–hydrogen bonds are broken. As a result, a
mixture of olefins, aromatic compounds, tar and gases is formed.
These products are cooled and separated into specific boiling-range
cuts of C1, C2, C3 and C4 compounds. The C4 fraction contains
butadiene, isobutylene, 1-butene, 2-butene and some other minor
hydrocarbons. The overall yields of butadiene during the process
depend on both the parameters of the process and the composition of
feedstocks. Generally, heavier steam-cracking feedstocks produce
greater amounts of butadiene. Separation and purification of
butadiene from other components is carried out mainly by an
extractive distillation process. The most commonly used solvents
are acetonitrile and dimethylformamide; dimethylacetamide, furfural
and N-methyl-2-pyrrolidinone have also been used to this end (Sun
& Wristers, 2002; Walther, 2003).
(ii) Dehydrogenation
The intentional dehydrogenation of n-butane or n-butenes also
yields butadiene. This is achieved by the Houdry process for
dehydrogenation of n-butane or by oxidative dehydrogenation of
n-butenes (Walther, 2003).
(iii) Ethanol-based production
A plant in India produces butadiene in a two-step process from
ethanol. Initial de-hydrogenation is achieved through a copper
catalyst, and the resulting mixture is then dehydrated at
atmospheric pressure in the presence of a zirconium oxide or
tantalum oxide–silica gel catalyst at 300–350 °C. Overall yields of
butadiene in the second reaction are about 70%. This process is
very similar to the adol condensation of acetaldehyde (Walther,
2003).
(b) Butadiene extraction processes
Regardless of the production process, final purification of
butadiene requires removal of any butane, butene or acetylene
impurities. Currently, seven different commercial
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50 IARC MONOGRAPHS VOLUME 97
processes exist for the extraction of butadiene that employ
different extraction solvents. The processes, identified by the
licencer and type of solvent, are: BASF Aktiengesellshaft —
N-methylpyrrolidone; Lyondell Petrochemical Company — acetonitrile;
Zeon Corp-oration — dimethylformamide; ConocoPhillips — furfural;
Shell Chemical Company — acetonitrile; Solutia —
β-methoxyproprionitrile with 15% furfural; Dow (formerly Union
Carbide Corporation) — dimethylacetamide; and (no licencer) —
cuprous ammonium acetate solution (Walther, 2003).
(c) Production volume
An estimated 9.3 million tonnes of butadiene were produced
worldwide in 2005 (CMAI, 2006). Production volumes for different
regions for the years 2004 and 2006 are given in Table 2.
World capacity grew by 3.5% per year between 1997 and 2002.
During that period, most of the increase in capacity occurred in
Asia, South America and the Middle East. Asia is now the largest
producer of butadiene, and accounts for one-third of the world
capacity (Walther, 2003).
Diepoxybutane is not believed to be produced commercially except
in small quan-tities for research purposes (National Library of
Medicine, 2008).
Table 2. Butadiene production (in tonnes) by world region from
1981 to 2006
Region 1981 1990 1996 2004 2006
North America 1480 1593 1956 2862 2878 South America – – – 377
377 Western Europe 636a 1256 1017b 1902 2232 Eastern Europe – – –
1170 736 Middle East/Africa – – – 180 340 Asia/Pacific 518c 1253
1755d 3104 4405
From IARC (1999), CMAI (2004, 2006) a No data available for
Germany b No data available for the United Kingdom or Italy c Value
for Japan only d No data available for China
1.2.2 Use
Butadiene is used primarily in the production of synthetic
rubbers and polymers. These polymers are used in a wide variety of
industrial and consumer products, to im-prove their functionality,
performance and safety and lower their costs. Butadiene-based
products are important components of automobiles, construction
materials, appliance
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1,3-BUTADIENE 51
parts, computers and telecommunications equipment, clothing,
protective clothing, pack-aging and household articles (White,
2007).
The synthetic rubbers that are produced from butadiene include
styrene–butadiene rubber, polybutadiene rubber, styrene–butadiene
latex, chloroprene rubber and nitrile rubber. Important plastics
that contain butadiene as a monomeric component are shock-resistant
polystyrene, a two-phase system that consists of polystyrene and
polybutadiene; polymers that consist of acrylonitrile, butadiene
and styrene; and a copolymer of methyl methacrylate, butadiene and
styrene, which is used as a modifier for poly(vinyl)chloride.
Butadiene is also used as an intermediate in the production of
chloroprene, adiponitrile and other basic petrochemicals (White,
2007).
Diepoxybutane has been proposed for use in curing polymers and
cross-linking textile fibres (National Library of Medicine,
2008).
1.3 Occurrence
1.3.1 Natural occurrence
Butadiene is not known to occur as a natural product.
1.3.2 Occupational exposure
According to the 1990–93 CAREX database (see General Remarks)
for 15 countries of the European Union (Kauppinen et al., 2000) and
the 1981–83 US National Occupational Exposure Survey (NOES, 1997),
approximately 31 500 workers in Europe and 50 000 workers in the
USA were potentially exposed to butadiene.
Based on data from CAREX, the major categories of industrial
exposure to butadiene in 15 European countries are the manufacture
of industrial chemicals (8000 persons), rubber products (7000
persons), plastic products (7000 persons), petroleum refining (2200
persons) and building construction (1600 persons) (Kauppinen et
al., 2000).
In the studies presented below, the accuracy of the levels of
exposure to butadiene measured with the methods used until the
mid-1980s may have been affected by the inability to distinguish
between butadiene and other C4 compounds, low desorption efficiency
at low concentrations, possible sample breakthrough in charcoal
tubes and possible loss during storage (Lunsford et al., 1990;
Bianchi et al., 1997).
(a) Petroleum refining and butadiene monomer production
Detailed industrial hygiene surveys were conducted in the USA by
the National Institute for Occupational Safety and Health in 1985
in four of 10 facilities where butadiene was produced by solvent
extraction of C4 fractions that originated from ethylene co-product
streams (Krishnan et al., 1987). Levels of butadiene to which
workers in various job categories were exposed are summarized in
Table 3. Jobs that required workers to handle or transport
containers, such as emptying sample cylinders or
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52 IARC MONOGRAPHS VOLUME 97
loading and unloading tank trucks or rail cars, presented the
greatest potential exposure. Geometric means of full-shift exposure
levels for other job categories were below 1 ppm [2.2 mg/m3].
Short-term samples showed that activities such as open-loop
sampling and emptying cylinders were associated with peak exposures
of 100 ppm [220 mg/m3]. Full-shift area samples indicated that
ambient concentrations of butadiene were greatest in the rail car
terminals (geometric mean, 1.8 ppm [3.9 mg/m3]) and in the tank
storage farm (2.1 ppm [4.7 mg/m3]).
Table 3. Eight-hour time-weighted average exposure levels in
personal breathing zone samples at four butadiene monomer
production faci-lities in the USA, 1985
Job category No. of samples
Exposure level (ppm [mg/m3])
Arithmetic mean
Geometric mean
Range
Process technician
Control room 10 0.45 [1.0] 0.09 [0.2] < 0.02–1.87 [<
0.04–4.1] Process area 28 2.23 [4.9] 0.64 [1.4] < 0.08–34.9
[< 0.18–77] Loading area Rail car 9 14.6 [32.4] 1.00 [2.2]
0.12–124 [0.27–273] Tank truck 3 2.65 [5.9] 1.02 [2.3] 0.08–5.46
[0.18–12.1] Tank farm 5 0.44 [0.97] 0.20 [0.44] < 0.04–1.53
[< 0.09–3.4] Laboratory technician Analysis 29 1.06 [2.3] 0.40
[0.88] 0.03–6.31 [0.07–14.0] Cylinder emptying 3 126 [277] 7.46
[16.5] 0.42–374 [0.93–826]
From Krishnan et al. (1987)
Monitoring in a plant in Finland generally indicated ambient air
levels of butadiene of less than 10 ppm [22 mg/m3] at different
sites (33 samples; mean sampling time, 5.3 h). In personal samples
for 16 process workers, the concentrations ranged from < 0.1 to
477 ppm [< 0.22–1050 mg/m3] (mean, 11.5 ppm [25 mg/m3]; median,
< 0.1 ppm [< 0.22 mg/m3]; 46 samples; mean sampling time, 2.5
h). The highest concentrations were measured during the collection
of samples, for which protective clothing and respirators were used
(Work Environment Fund, 1991).
A study of biological monitoring for the mutagenic effects of
exposure to butadiene reported estimated average exposures of 1 ppm
[2.2 mg/m3] for workers in a butadiene monomer plant. Ambient air
concentrations in production areas averaged 3.5 ppm [7.7 mg/m3],
while average concentrations of 0.03 ppm [0.07 mg/m3] were reported
for the control area (Ward, J.B. et al., 1996).
Levels of exposure to butadiene of workers in various job groups
in the production and distribution of gasoline (see IARC, 1989) are
shown in Table 4. Table 5 shows exposures in 1984–87 of workers in
different areas of petroleum refineries and
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1,3-BUTADIENE 53
Table 4. Personal exposures to butadiene associated with
gasoline in 1984–85 in 13 European countriesa (540
measurements)
Activity Exposure level (mg/m3)
Arithmetic mean
Range Duration (TWA)
Production on-site (refining) 0.3 ND–11.4 8 h Production
off-site (refining) 0.1 ND–1.6 8 h Loading ships (closed system)
6.4 ND–21.0 8 h Loading ships (open system) 1.1 ND–4.2 8 h Loading
barges 2.6 ND–15.2 8 h Jetty man 2.6 ND–15.9 8 h Bulk loading road
tankers Top loading < 1 h 1.4 ND–32.3 < 1 h Top loading >
1 h 0.4 ND–4.7 8 h Bottom loading < 1 h 0.2 ND–3.0 < 1 h
Bottom loading > 1 h 0.4 ND–14.1 8 h Road tanker delivery (bulk
plant to service station) ND Rail car top loading 0.6 ND–6.2 8 h
Drumming ND Service station attendant (dispensing fuel) 0.3 ND–1.1
8 h Self-service station (filling tank) 1.6 ND–10.6 2 min
From CONCAWE (1987) ND, not detected; TWA, time-weighted average
a Countries included not reported
Table 5. Eight-hour time-weighted average concentrations of
butadiene to which workers in different jobs in petroleum
refineries and petrochemical facilities were exposed in the USA,
1984–87
Job area No. of facilities
Arithmetic meana Range
ppm mg/m3 ppm mg/m3
Production 7 0.24 0.53 0.008–2.0 0.02–4.4 Maintenance 6 0.11
0.24 0.02–0.37 0.04–0.82 Distribution 1 2.90 6.41 – – Laboratory 4
0.18 0.40 0.07–0.4 0.16–0.88
From Heiden Associates (1987) a Weighted by number of exposed
workers
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54 IARC MONOGRAPHS VOLUME 97
petrochemical facilities where crude butadiene was produced
(usually a C4 stream obtained as a by-product of ethylene
production). Table 6 shows more recent data on crackers at
butadiene production plants for the years 1986–93 (ECETOC,
1997).
Exposure data from 15 monomer extraction sites for the years
1984–93 showed that less than 10% of the measured concentrations
exceeded 5 ppm [11 mg/m3] (Table 7); in 1995 (Table 8), personal
exposure levels in general were below 5 ppm [11 mg/m3] (ECETOC,
1997).
In 1998, personal exposure to butadiene was measured for 24
workers in a monomer production facility in the Czech Republic. The
mean (± standard deviation [SD]) concentration of butadiene,
calculated from 217 individual time-weighted average (TWA)
measurements, was 0.6 ± 2.1 mg/m3 [0.27 ± 0.95 ppm]. The personal
TWA measure-ments from all monomer production workers ranged from
undetectable to 19.9 mg/m3. The mean concentration for the control
group was 0.03 ± 0.03 mg/m3 [0.01 ± 0.01 ppm], calculated from 28
personal TWA exposure measurements (Albertini et al., 2003a).
Personal exposure to butadiene of 10 workers who held different
jobs in a petrochemical plant in Finland was assessed using passive
monitors shortly after the threshold limit value (TLV) of 1 ppm had
come into force. A total of 119 personal breathing zone samples
were taken and 117 were analysed. Of these, 32 (27%) samples were
under the limit of quantification (0.029 mg/m3 [0.013 ppm] in a
20.5-L sample), 81 samples (69%) were between the limit of
quantification and 1 ppm [2.2 mg/m3] and four samples (3%) were
over the Finnish occupational exposure limit of 1 ppm. The mean
value of all samples was 0.17 ppm [0.38 mg/m3] and the mean value
of the samples that exceeded the Finnish occupational exposure
limit was 1.75 ppm [3.87 mg/m3]. The mean level of exposure varied
significantly (p = 0.03) between the 10 workers. Smoking did not
significantly affect the values, but the seasonal effect was
significant (p = 0.02) (Anttinen-Klemetti et al., 2004).
The occupational exposure of 42 workers in a petrochemical plant
in Italy where butadiene was produced and used to prepare polymers
was assessed by biomonitoring. The control group originated from
the same industrial complex and included 43 workers who had no
significant occupational exposure to butadiene. Active sampling
from the breathing zone of the workers was performed during a full
shift. Each exposed worker was assessed three to four times over a
period of 6 weeks during different shifts. The mean exposure level
of the control group was 0.9 µg/m3 [0.4 ppb] (SD, 1.0) and the
lowest and highest values were < 0.1 and 3.8 µg/m3 [< 0.05
and 1.7 ppb], respectively. The mean exposure level of the exposed
group was 11.5 µg/m3 [5.2 ppb] (SD, 35.8) and the lowest and
highest values were < 0.1 and 220.6 µg/m3 [< 0.04 and 99.8
ppb], respectively (Fustinoni et al., 2004).
An exposure assessment was carried out in southern Taiwan,
China, on a 120-acre [486 000 m2] petrochemical complex that
comprised 11 different manufacturing plants. Butadiene was produced
in two of the plants, which had an annual production of about 156
000 tonnes per year. Using the Fourier transform infrared
spectroscopy technique, data were collected on 77 days during the
period 1997–99. The relative number of samples that
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1
,3-B
UT
AD
IEN
E
55
Table 6. Personal exposures to butadiene of crackers in
butadiene production plants in the European Union
Job category Exposure level (ppm)
Year of measurement
No. of workers
No. of samples
< 1 1–2 2–3 3–4 4–5 5–10 10–25 ≥ 25
Unloading, loading, storage
1986–92 210 92 82 3 3 2 0 0 1 0
Distillation (hot) 1986–93 394 92 382 0 3 1 2 0 2 2
Laboratory, sampling
1986–93 132 184 178 2 1 2 1 0 0 0
Maintenance 1986–92 282 371 364 5 0 1 0 0 1 0
Other 1990–92 467 509 487 18 2 1 1 ND 0 0
Total 1986–93 1485 1548 1493 28 9 8 4 0 4 2
From ECETOC (1997)
ND, not detected [limit of detection not stated]
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56
IAR
C M
ON
OG
RA
PH
S V
OL
UM
E 9
7
Table 7. Personal exposures to butadiene in extraction unitsa of
butadiene production plants in the European Union
Job category Year of measurement
No. of workers
No. of samples
Exposure level (ppm)
< 1 1–2 2–3 3–4 4–5 5–10 10–25 ≥ 25
Unloading, loading, storage
1986–93 392 224 178 9 8 7 2 11 22 7
Distillation (hot) 1985–93 256 626 535 20 19 6 11 8 12 15
Laboratory, sampling 1985–93 45 48 29 4 2 2 2 3 5 1
Maintenance 1986–93 248 127 93 14 3 2 1 3 4 7
Other 1984–92 45 10 8 2 0 0 0 0 0 0
Total 1984–93 986 1035 843 49 32 17 16 25 23 30
From ECETOC (1997) a Isolation of butadiene from C4 stream
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1,3-BUTADIENE 57
Table 8. Personal exposures to butadiene at 15 monomer
extraction sites in the European Union in 1995
Job category Exposure level (ppm)
Time-weighted averages
Range of values
Production Extraction Derivationa
< 0.01–2 1.4–3.4
0–14 0.07–60
Storage and filling < 0.02–5 0–18.1 Transport < 0.1–0.7
0.02–1.2 Laboratory 0.03–1 0–13.1
From ECETOC (1997) a Integrated monomer extraction and
styrene–butadiene production on same site
were above the detection limit was 15.2% and the mean value of
the measurements was 10.5 ± 36.7 ppb [23.2 ± 81.1 µg/m3]. The
maximum concentration measured was 3.1 ppm [6.8 mg/m3] (Chan et
al., 2006). [Measurements were area samples and may under-estimate
exposure of the workers.]
In the monomer industry, potential exposure to compounds other
than butadiene includes exposure to extraction solvents and
components of the C4 feedstock. Extraction solvents differ between
facilities: common solvents include dimethylformamide,
di-methylacetamide, acetonitrile, β-methoxypropionitrile (Fajen,
1985a), furfural and aqueous cuprous ammonium acetate (Occupational
Safety and Health Administration, 1990b). Stabilizers are commonly
used to prevent the formation of peroxides in air and during
polymerization. No information was available on these exposures or
on exposure to chemicals other than butadiene that are produced in
some facilities such as butylenes, ethylene, propylene,
polyethylene and polypropylene resins, methyl-tert-butyl ether and
aromatic hydrocarbons (Fajen, 1985b,c).
(b) Production of polymers and derivatives
In samples taken at a styrene–butadiene rubber plant in the USA
in 1976 (Table 9), levels of butadiene above 100 ppm [220 mg/m3]
were encountered by technical services personnel (115 ppm [253
mg/m3]) and an instrument man (174 ppm [385 mg/m3]; Meinhardt et
al., 1978). At another styrene–butadiene rubber manufacturing plant
in the USA in 1979, the only two departments in which levels were
greater than 10 ppm [22 mg/m3] were the tank farm (53.4 ppm [118
mg/m3]) and maintenance (20.7 ppm [46 mg/m3]; Checkoway &
Williams, 1982). Overall mean 8-h TWA exposure levels differed
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58 IARC MONOGRAPHS VOLUME 97
Table 9. Eight-hour time-weighted average exposure levels of
butadiene measured in two styrene–butadiene rubber manufacturing
plants in the USA
Reference Year of sampling
Job classification or department
No. of samples
Exposure level
ppm mg/m3
Meinhardt 1976 Instrument man 3 58.6 130 et al. (1978) Technical
services personnel 12 19.9 43.9 Head production operator 5 15.5
34.3 Carpenter 4 7.80 17.2 Production operator 24 3.30 7.29
Maintenance mechanic 17 3.15 6.96 Common labourer 17 1.52 3.36
Production foreman 1 1.16 2.56 Operator helper 3 0.79 1.75 Pipe
fitter 8 0.74 1.64 Electrician 5 0.22 0.49
Checkoway & 1979 Tank farm 8 20.0 44.3 Williams (1982)
Maintenance 52 0.97 2.1 Reactor recovery 28 0.77 1.7 Solution 12
0.59 1.3 Factory service 56 0.37 0.82 Shipping and receiving 2 0.08
0.18 Storeroom 1 0.08 0.18
considerably between the two plants: 13.5 ppm [30 mg/m3] and
1.24 ppm [2.7mg/m3], respectively (Meinhardt et al., 1982).
Detailed industrial hygiene surveys were conducted in 1986 in
five of 17 facilities in the USA where butadiene was used to
produce styrene–butadiene rubber, nitrile–butadiene rubber,
polybutadiene rubber, neoprene and adiponitrile (Fajen, 1988).
Levels of butadiene to which workers in various job categories were
exposed are summarized in Table 10. Process technicians in
unloading, in the tank farm and in the purification, polymerization
and reaction areas, laboratory technicians and maintenance
technicians were exposed to the highest levels. Short-term sampling
showed that activities such as sampling a barge and laboratory work
were associated with peak exposures of more than 100 ppm [220
mg/m3]. Full-shift area sampling indicated that geometric mean
ambient concentrations of butadiene were less than 0.5 ppm [1.1
mg/m3] and usually less than 0.1 ppm [0.22 mg/m3] in all locations
measured at the five plants.
A biological monitoring study that used personal sampling
reported average levels of butadiene of 0.30, 0.21 and 0.12 ppm
[0.66, 0.46 and 0.27 mg/m3] for the high-, inter-mediate- and
low-exposure groups, respectively, in a styrene–butadiene rubber
plant in Texas, USA (Ward, J.B. et al., 1996).
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1,3-BUTADIENE 59
Table 10. Eight-hour time-weighted average exposure levels in
personal breathing zone samples at five plants that produced
butadiene-based polymers and derivatives in the USA, 1986
Job category No. of samples
Exposure level (ppm [mg/m3])
Arithmetic mean
Geometric mean
Range
Process technician Unloading area 2 14.6 [32.27] 4.69 [10.37]
0.770–28.5 [1.7–63.0] Tank farm 31 2.08 [4.60] 0.270 [0.60] <
0.006–23.7 [< 0.01–2.4] Purification 18 7.80 [17.24] 6.10
[13.48] 1.33–24.1 [3.0–53.3] Polymerization or reaction 81 0.414
[0.92] 0.062 [0.14] < 0.006–11.3 [< 0.01–5.0] Solutions and
coagulation 33 0.048 [0.11] 0.029 [0.06] < 0.005–0.169 [<
0.01–4] Crumbing and drying 35 0.033 [0.07] 0.023 [0.05] <
0.005–0.116 [< 0.01–0.26] Packaging 79 0.036 [0.08] 0.022 [0.05]
< 0.005–0.154 [< 0.01–0.34] Warehouse 20 0.020 [0.04] 0.010
[0.02] < 0.005–0.068 [< 0.01–0.15] Control room 6 0.030
[0.07] 0.019 [0.04] < 0.012–0.070 [< 0.03–0.16] Laboratory
technician 54 2.27 [5.02] 0.213 [0.47] < 0.006–37.4 [<
0.01–82.65] Maintenance technician 72 1.37 [3.02] 0.122 [0.27] <
0.006–43.2 [< 0.01–95.47] Utilities operator 6 0.118 [0.26]
0.054 [0.12] < 0.006–0.304 [< 0.01–0.67]
From Fajen (1988)
In 13 of 27 European sites where styrene–butadiene rubber and
styrene–butadiene latex were produced, less than 10% of the
concentrations measured exceeded 5 ppm (Table 11; ECETOC,
1997).
Data from the Netherlands are available from 1976 onwards, but
the measurement methods used in the early surveys are unknown
(Kwekkeboom, 1996; Dubbeld, 1998). No clear trend can be seen for
the years 1990–97, but average exposures were relatively low
(arithmetic mean < 3 ppm [6.6 mg/m3]) (Table 12).
Exposure of 38 workers was measured in a butadiene polymer
production facility in China. Personal full-shift measurements
established that workers in butadiene operations were exposed to a
median level of 2.0 ppm [4.4 mg/m3]. Short-term breathing zone
measurements of butadiene showed great extremes in exposure; DMF
[dimethyl-formamide] analysts had a median exposure of 54 ppm [119
mg/m3] (range, below detec-tion to 3090 ppm [6829 mg/m3]; 50
samples), polymer analysts had a median exposure of 6.5 ppm [14.4
mg/m3] (range, below detection to 1078 ppm [2382 mg/m3]; 41
samples) and maintenance-recovery workers had a median exposure of
7.0 ppm [15.5 mg/m3] (range, below detection to > 12 000 ppm
[> 26 520 mg/m3]; 24 samples) (Hayes et al., 2001).
A biomonitoring study carried out in a styrene–butadiene rubber
plant in Southeast Texas, in which 37 workers were monitored during
their entire work shift using passive samplers, demonstrated that
levels in the tank area exceeded the current Occupational
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60
IAR
C M
ON
OG
RA
PH
S V
OL
UM
E 9
7
Table 11. Eight-hour time-weighted average personal exposures to
butadiene in styrene–butadiene rubber plants in the European Union
(1984–93)
Job category Exposure level (ppm)
No. of workers
No. of samples
< 0.5 0.51–1 1.01–2 2.01–3 3.01–4 4.01–5 5.01–10 10.01–25 ≥
25
Unloading, loading and storage
132 77 47 1 8 6 3 0 5 5 2
Polymerization 324 147 61 23 25 18 6 4 7 3 0
Recovery 103 165 113 9 9 14 7 4 5 4 0
Finishing 247 120 90 16 3 4 5 1 1 0 0
Laboratory sampling
115 113 68 13 12 6 4 2 3 5 0
Maintenance 141 39 28 1 2 1 1 2 1 2 1
Total 1062 661 407 63 59 49 26 13 22 19 3
From ECETOC (1997)
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1,3-BUTADIENE 61
Table 12. Eight-hour time-weighted average exposure levels of
butadiene in personal breathing zone samples at a plant that
produced styrene–butadiene polymer in the Netherlands, 1990–97
Year No. of samples
Exposure level (mg/m3 [ppm])
Arithmetic mean
Range Methoda
1990 27 5.45 [2.47] 0.35–69.06 [0.16–31.24] 3M 3500 1991 19 1.11
[0.50] 0.09–2.88 [0.04–1.30] NIOSH 1024 1992 23 2.79 [1.26]
0.13–11.78 [0.06–5.33] 3M 3520 1993 38 2.87 [1.30] 0.15–13.13
[0.07–5.94] 3M 3520/
NIOSH 1024 1996/97 process operators 20 2.77 [1.25] 0.13–46.62
[0.06–21.10] 3M 3520 1996/97 maintenance workers 14 0.54 [0.24]
0.12–9.89 [0.05–4.48] 3M 3520
From Kwekkeboom (1996); Dubbeld (1998) a Analytical methods used
are described by Bianchi et al. (1997). Methods 3M 3500 and 3M 3520
involve absorption onto butadiene-specific activated charcoal,
followed by desorption with carbon disulfide or with
dichloromethane, respectively, and analysis by direct-injection gas
chromato-graphy with flame ionization detection.
Safety and Health Administation permissible exposure limit for
butadiene. However, the workers wore protective equipment on this
particular job. TWA values in various work areas are summarized in
Table 13 (Ward et al., 2001).
In 1998, 319 personal workshift TWA measurements of exposure to
butadiene were obtained for 34 workers in a polymer production
plant in the Czech Republic. The mean (± SD) concentration of
butadiene was 1.8 ± 4.7 mg/m3 [0.8 ± 2.1 ppm]. The individual TWA
measurements from all polymer production workers ranged from 0.002
to 39.0 mg/m3 [0.001–17.6 ppm]. The level of exposure of the
control group was 0.03 ± 0.03 mg/m3 [0.01 ± 0.01 ppm], calculated
from 28 personal TWA measurements (Albertini et al., 2003a).
A Finnish study assessed personal exposure to butadiene in three
plants that manu-factured styrene–butadiene latex. Full-shift air
samples were collected from the breathing zone of 28 workers using
passive samplers over 4 months. A total of 885 samples were
collected and the number of samples per participant ranged from 19
to 39. Samples were collected at the same time in all three plants.
The data showed that 624 (70.5%) of the samples were below the
limit of quantification; 240 (27.1%) samples were between the limit
of quantification and 1 ppm [2.2 mg/m3] and 21 (2.4%) were over the
Finnish occupational exposure limit of 1 ppm [2.2 mg/m3]. Mean
butadiene concentrations in the three plants were 0.068, 0.125 and
0.302 ppm [0.15, 0.28 and 0.67 mg/m3], respectively.
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62 IARC MONOGRAPHS VOLUME 97
Table 13. Time-weighted average exposures to butadiene in a
styrene–butadiene rubber plant in the USA, 1998
Work area Subjects Detectable samples
Samples below the LODa
Exposure level (mean ± SD) (ppm [mg/m3])
Tank farm 6 17 0 4.04 ± 3.45 [8.9 ± 7.6] Recovery 6 17 0 1.09 ±
2.35 [2.41 ± 5.19] Reactor 9 17 3 0.64 ± 1.26 [1.41 ± 2.78] Low
areasb 14 22 19 0.05 ± 0.06 [0.11 ± 0.13] Laboratory 1 2 0 0.29 ±
0.33 [0.64 ± 0.73] Blending 1 3 0 0.49 ± 0.24 [1.08 ± 0.53]
From Ward et al. (2001) LOD, limit of detection; SD, standard
deviation a Half of the 0.002 ppm detection limit was used to
calculate exposure to butadiene for the samples b Coagulation,
baling, packing, water paint, shipping, warehouse and control
room
Statistical analysis of the data did not indicate any
significant difference between the plants when all results were
considered (Anttinen-Klemetti et al., 2006).
In a Czech study that included 26 female control workers, 23
female butadiene-exposed workers, 25 male control workers and 30
male butadiene-exposed workers, 10 personal full-shift (8-h)
measurements per worker over a 4-month period showed mean 8-h TWA
exposure levels of 0.008 mg/m3 and 0.4 mg/m3 [0.004 and 0.18 ppm]
for control and exposed women, respectively. The highest single 8-h
TWA value among exposed women was 9.8 mg/m3 [4.5 ppm]. Mean 8-h TWA
exposure levels were 0.007 mg/m3 and 0.8 mg/m3 [0.003 and 0.36 ppm]
for control and exposed men, respectively; personal single 8-h TWA
values of up to 12.6 mg/m3 [5.7 ppm] were measured in the exposed
group. The concentrations for butadiene-exposed workers were
significantly higher than those for the controls for both men and
women; the concentrations for butadiene-exposed workers were
significantly higher for men than for women (Albertini et al.,
2007). [The difference in exposure levels may be due to differences
in tasks performed by men and women.]
Data from a Canadian styrene–butadiene rubber plant indicate a
clear decrease in exposure from 1977 to 1991 (Sathiakumar &
Delzell, 2007; Table 14). The data were used to validate the
estimates of historical exposure to butadiene (Macaluso et al.,
1996, 2004; Sathiakumar et al., 2007).
The manufacture of butadiene-based polymers and butadiene
derivatives implies potential exposure to a number of other
chemical agents that vary according to product and process and
include other monomers (styrene, acrylonitrile, chloroprene),
solvents, additives (e.g. activators, antioxidants, modifiers),
catalysts, mineral oils, carbon black, chlorine, inorganic acids
and caustic solutions (Fajen, 1986a,b; Roberts, 1986). Styrene,
benzene and toluene levels were measured in 1979 in various
departments of a plant that
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1,3-BUTADIENE 63
manufactured styrene–butadiene rubber in the USA: mean 8-h TWA
levels of styrene were below 2 ppm [8.4 mg/m3], except for
tank-farm workers (13.7 ppm [57.5 mg/m3], eight samples); mean
benzene levels did not exceed 0.1 ppm [0.3 mg/m3], and those of
toluene did not exceed 0.9 ppm [3.4 mg/m3] (Checkoway &
Williams, 1982). Meinhardt et al. (1982) reported that the mean 8-h
TWA levels of styrene in two styrene–butadiene rubber manufacturing
plants were 0.94 ppm [3.9 mg/m3] (55 samples) and 1.99 ppm [8.4
mg/m3] (35 samples) in 1977; the average level of benzene measured
in one of the plants was 0.1 ppm [0.3 mg/m3] (three samples).
Average levels of styrene, toluene, benzene, vinyl cyclohexene and
cyclooctadiene were reported to be below 1 ppm in another
styrene–butadiene rubber plant in 1977 (Burroughs, 1977).
Dimethyldithiocarbamate has been used in some plants and dermal
exposure to this compound potentially exists (Delzell et al.,
2001).
Table 14. Exposure levels of butadiene in a styrene–butadiene
rubber plant in Canada
Year No. of jobs monitored
No. of measurements
Exposure level (meana ± SD ) (ppm [mg/m3])
1977 3 56 24.8 ± 69.9 [54.8 ± 154.5] 1978 11 527 16.0 ± 166.6
[35.4 ± 368.2] 1979 13 274 10.6 ± 153.2 [23.4 ± 338.6] 1980 13 301
14.5 ± 137.8 [32.0 ± 304.5] 1981 15 307 4.8 ± 38.4 [10.6 ± 84.9]
1982 21 406 3.8 ± 28.2 [8.4 ± 62.3] 1983 13 113 3.9 ± 19.4 [8.6 ±
42.9] 1984 27 658 2.5 ± 20.3 [5.5 ± 44.9] 1985 27 482 2.6 ± 18.4
[5.7 ± 40.7] 1986 30 504 2.3 ± 16.2 [5.08 ± 35.8] 1987 26 310 0.85
± 6.3 [1.9 ± 13.9] 1988 28 417 1.0 ± 5.2 [2.2 ± 11.5] 1989 27 238
1.5 ± 5.5 [3.3 ± 12.2] 1990 27 223 0.63 ± 3.3 [1.4 ± 7.3] 1991 25
162 0.34 ± 0.61 [0.75 ± 1.35]
From Sathiakumar et al. (2007) SD, standard deviation a Weighted
by the number of measurements for job/year combinations in a
year
(c) Manufacture of rubber and plastics products
In a tyre and tube manufacturing plant in the USA in 1975, a
cutter man/Banbury operator was reported to have been exposed to
2.1 ppm [4.6 mg/m3] butadiene (personal 6-h sample) (Ropert,
1976).
Personal 8-h TWA measurements taken in 1978 and 1979 in
companies where acrylonitrile–butadiene–styrene moulding operations
were conducted showed levels of
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64 IARC MONOGRAPHS VOLUME 97
< 0.05–1.9 mg/m3 [< 0.11–4.2 ppm] (Burroughs, 1979;
Belanger & Elesh, 1980; Ruhe & Jannerfeldt, 1980).
In a polybutadiene rubber warehouse, levels of 0.003 ppm [0.007
mg/m3] butadiene were found in area samples; area and personal
samples taken in tyre plants revealed levels of 0.007–0.05 ppm
[0.016–0.11 mg/m3] butadiene (Rubber Manufacturers’ Association,
1984).
Unreacted butadiene was detected as a trace (0.04–0.2 mg/kg) in
15 of 37 bulk samples of polymers and other chemicals synthesized
from butadiene and analysed in 1985–86. Only two samples contained
measurable amounts of butadiene: tetrahydro-phthalic anhydride (53
mg/kg) and vinylpyridine latex (16.5 mg/kg) (JACA Corp., 1987).
Detailed industrial hygiene surveys were conducted in 1984–87 in
the USA at a rubber tyre plant and an industrial hose plant where
styrene–butadiene rubber, poly-butadiene and
acrylonitrile–butadiene rubber were processed. No butadiene was
detected in any of 124 personal full-shift samples from workers in
the following job categories that were identified as involving
potential exposure to butadiene: Banbury operators, mill operators,
extruder operators, curing operators, conveyer operators,
calendering operators, wire winders, tube machine operators, tyre
builders and tyre repair and buffer workers (Fajen et al.,
1990).
Occupational exposures to many other agents in the rubber goods
manufacturing industry have been reviewed previously (IARC,
1982).
(d) Comparison of exposure levels in monomer and
styrene–butadiene rubber production facilities
Exposures measured in monomer production facilities in the USA
demonstrated overall mean levels of 3.5 ppm [7.7 mg/m3] (measured
in 1979–92; number not reported; stationary sampling; Cowles et
al., 1994) and 7.1 ppm [15.7 mg/m3] (measured in 1985; 87 samples;
personal sampling; Krishnan et al., 1987). Recently reported values
from the Czech Republic and Finland were 0.64 ppm [1.41 mg/m3]
(measured in 1998; 217 samples; personal sampling) and 0.17 ppm
[0.38 mg/m3] (measured in 2002; 117 samples; personal sampling)
(Albertini et al., 2003a; Anttinen-Klemetti et al., 2004).
Measurement of butadiene concentrations in a styrene–butadiene
rubber plant in Canada demonstrated a decrease in exposure during
the 14 years of monitoring. The levels dropped from 24.8 ppm in
1977 [54.8 mg/m3] to 0.34 ppm [0.75 mg/m3] in 1991 (Table 14)
(Sathiakumar et al., 2007).
The decreasing trend of exposure was apparent in both monomer
and styrene–butadiene rubber production; however, the lack of data
from the 1940s to the 1970s does not allow comparison between the
two processes.
1.3.3 Environmental occurrence
According to the Environmental Protection Agency Toxic Chemical
Release Inventory in the USA, industrial releases of butadiene to
the atmosphere from industrial
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1,3-BUTADIENE 65
facilities in the USA were 4425 tonnes in 1987, 2360 tonnes in
1990 and 1385 tonnes in 1995. According to the same database,
fugitive air emissions were 157 973 kg and point source air
emissions were 450 926 kg in 2005 (Environmental Protection Agency
Toxic Release Inventory, 2005; National Library of Medicine,
2008).
Under laboratory conditions, non-catalyst vehicles emitted
butadiene at a rate of 20.7 ± 9.2 mg/kg. Vehicles that had a
functioning catalyst–emission control device had an average
emission rate of 2.1 ± 1.5 mg/km. Based on these numbers, the
authors concluded that vehicle emissions of butadiene have been
substantially underestimated (Ye et al., 1997). Based on an average
of 20 000 km per year per car and approximately 243 million
registered cars in the USA in 2004, and considering the average
emission rates estimated by Ye et al. (1997), emissions of
butadiene from automobile exhausts can be estimated to amount to
approximately 106 770 tonnes per year.
Butadiene is also released to the atmosphere from the smoke of
bush fires, the thermal breakdown or burning of plastics and by
volatization from gasoline (Agency for Toxic Substances and Disease
Registry, 1992; see IARC, 1992).
Kim et al. (2001, 2002) measured the concentrations of 15
volatile organic com-pounds, including butadiene, in a wide range
of urban micro-environments in the United Kingdom (Table 15) and
estimated the personal exposure of 12 urban dwellers directly and
indirectly via static monitoring combined with a personal
activities diary (Table 16).
Table 15. Mean concentrations of butadiene in micro-environments
in the United Kingdom
Environment No. of samples Concentration (mean ± SD) (µg/m3)
Home 64 1.1 ± 1.9 Office 12 0.3 ± 0.2 Restaurant 6 1.5 ± 0.8
Public house 6 3.0 ± 2.0 Department store 8 0.6 ± 0.4 Cinema 6 0.6
± 0.3 Perfume store 3 0.9 ± 0.1 Library 6 0.4 ± 0.2 Laboratory 8
0.2 ± 0.1 Train station 12 2.2 ± 1.7 Coach station 12 0.9 ± 0.7
Road with traffic 12 1.8 ± 0.9 Car 35 7.9 ± 4.7 Train 18 1.0 ± 0.6
Bus 18 1.7 ± 0.9 Smoking home 32 1.7 ± 2.5 Nonsmoking home 32 0.5 ±
0.3
From Kim et al. (2001) SD, standard deviation
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66 IARC MONOGRAPHS VOLUME 97
Table 16. Daytime and night-time concentrations (µg/m3) of
butadiene recorded during personal exposure monitoring in the
United Kingdom, 1999–2000
Period No. of samples
Mean Standard deviation
Minimum Maximum
Daytime 473 1.1 0.4 ND 26.3 Night-time 99 0.8 0.4 ND 7.9
From Kim et al. (2002) ND, not detected
Environmental exposure to emissions, including butadiene, was
compared between bus and cycling commuters on a route in Dublin.
Samples were collected during both morning and afternoon rush-hour
periods using continuous sampling. The average concentrations
experienced by the cyclist and the bus passenger for all journeys
were 0.47 ppb [103 µg/m3] (SD, 0.19; min., 0.24; max., 0.81) and
0.78 ppb [1.7 µg/m3] (SD, 0.34; min., 0.34; max., 1.49),
respectively (O’Donoghue et al., 2007).
In the United Kingdom, the estimated emission of butadiene in
1996 was 10.6 thousand tonnes. Road vehicle exhaust emissions
dominated and comprised 68% of the total emissions, while emissions
from off-road vehicles and machinery accounted for 14%. The
remaining emissions arose from the chemical industry, during the
manufacture of butadiene and its use in the production of various
rubber compounds. These two processes accounted for 8 and 10%,
respectively, of total emissions in the United King-dom in 1996
(Dollard et al., 2001).
Municipal structural fires are a source of butadiene, and the
mean level of butadiene from nine fires ranged from 0.03 to 4.84
ppm [0.07–9.9 mg/m3] (Austin et al., 2001). Domestic wood burning
also has an impact on levels of butadiene in homes. Wood burners
had a significantly higher personal exposure to butadiene (median,
0.18 µg/m3) than the reference group. Similarly, significantly
higher indoor levels were reported (median, 0.23 µg/m3) in homes of
wood burners than in the homes of the reference group (Gustafson et
al., 2007).
The intake of butadiene that results from exposure to
environmental tobacco smoke for a person who lives with one or more
smokers in homes where smoking is permitted was estimated to be in
the range of 16–37 µg per day (Nazaroff & Singer, 2004). The
levels of butadiene in public houses in Dublin were assessed before
and after the smoking ban in 2004. The average level before the ban
was 4.15 µg/m3 [1.87 ppb]. The levels of butadiene recorded in the
same establishments when cigarettes were no longer being smoked
dropped significantly to 0.22 µg/m3 [0.1 ppb], which is still
higher than the average ambient level (0.12 µg/m3 [0.05 ppb])
(McNabola et al., 2006).
In the metropolitan area of Mexico City, three persons who were
simultaneously monitored for butadiene inside the home and outdoors
had median levels of 2.1 µg/m3 [1 ppb] (max., 11.5 µg/m3 [5.2
ppb]), 2.0 µg/m3 [0.9 ppb] (max., 8.3 µg/m3 [3.7 ppb]) and
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1,3-BUTADIENE 67
0.8 µg/m3 [0.4 ppb] (max., 4.6 µg/m3 [2.1 ppb]) for personal,
indoor and outdoor ex-posure, respectively (Serrano-Trespalacios et
al., 2004).
Ambient concentrations of butadiene were measured in Japan
during the years 1997–2003 at general environmental stations,
roadside stations and industrial vicinity stations. The mean levels
in 1998 were 0.28, 0.56 and 0.37 µg/m3 [0.13, 0.25 and 0.17 ppb]
for the general environment, roadside and industrial vicinity,
respectively. The overall level was 0.36 µg/m3 [0.16 ppb]. In 2003,
corresponding levels were 0.22, 0.42 and 0.31 µg/m3 [0.10, 0.19 and
0.14 ppb], with an overall level of 0.29 µg/m3 [0.13 ppb]
(Higashino et al., 2006).
Mainstream and sidestream cigarette smoke contain approximately
20–40 µg and 80–130 µg butadiene per cigarette, respectively;
levels of butadiene in smoky indoor environ-ments are typically
10–20 µg/m3 [5–9 ppb] (IARC, 2004).
Based on its physical and chemical properties, butadiene is
unlikely to be detected in water or in soil (Agency for Toxic
Substances and Disease Registry, 1992).
1.4 Regulations and guidelines
Occupational exposure limits and guidelines for butadiene in
several countries, regions or organizations are given in Table
17.
The government of the United Kingdom has imposed an air quality
standard for butadiene of 2.25 µg/m3 [1.00 ppb] to be achieved by
December 2003 (running annual mean) (AEA Energy & Environment,
2002).
Table 17. Occupational exposure limits and guidelines for
butadiene in several countries/regions or organizations
Country/region or organization
TWA (ppm)a
STEL (ppm)a
Carcinogenicityb
Notes
Belgium 2 Ca Brazil 780 Canada Alberta
2
Schedule 2
British Columbia 2 2 K2 Ontario 5 Quebec 2 A2 China (mg/m3) 5
12.5 STEL based on the
‘ultra limit coefficient’ China, Hong Kong SAR 2 A2 Czech
Republic (mg/m3) 10 20 Finland 1 Germany-MAK 1 Ireland 1 Ca2
Japan-JSOH 1 Malaysia 2
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68 IARC MONOGRAPHS VOLUME 97
Table 17 (contd)
Country/region or organization
TWA (ppm)a
STEL (ppm)a
Carcinogenicityb
Notes
Mexico 1000 1250 A2 Netherlands 21 Ca New Zealand 10 A2 Norway 1
Ca Poland-MAC (mg/m3) 10 40 South Africa-DOL CL 10 Spain 2 Ca1
Sweden 0.5 5 Ca United Kingdom 10 R45 USA ACGIH (TLV)
2
A2
Cancer
NIOSH IDLH (ceiling) 2000 Ca OSHA PEL 1 5
From ACGIH® Worldwide (2005) ACGIH, American Conference of
Governmental Industrial Hygienists; DOL CL, Department of Labour –
ceiling limits; IDLH, immediately dangerous to life or health;
JSOH, Japanese Society of Occupational Health; MAC, maximum
acceptable concentration; MAK, maximum allowed concen-tration;
NIOSH, National Institute for Occupational Safety and Health; OSHA,
Occupational Safety and Health Administration; PEL, permissible
exposure limit; STEL, short-term exposure limit; TLV, threshold
limit value; TWA, time-weighted average a Unless otherwise
specified b Ca (Belgium, Netherlands, Sweden, NIOSH),
carcinogen/substance is carcinogenic; Ca (Norway), potential
cancer-causing agent; 2, considered to be carcinogenic to humans;
A2, suspected human carcinogen/carcinogenicity suspected in humans;
1, substance which causes cancer in man/carcino-genic to humans;
Ca2, suspected human carcinogen; Ca1, known or presumed human
carcinogen; R45, may cause cancer
2. Studies of Cancer in Humans
2.1 Background
Over the last 30 years, the relationship between exposure to
butadiene and cancer in human populations has been investigated in
numerous studies. The most relevant investigations focused on
working populations who were employed in butadiene monomer and
styrene–butadiene rubber production.
Three independent cohorts of monomer production workers in the
USA have been studied: at two Union Carbide plants in West Virginia
(Ward et al., 1995), at a Texaco plant in Texas (Divine &
Hartman, 2001) and at a Shell plant in Texas (Tsai et al.,
2001).
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1,3-BUTADIENE 69
Two independent groups of styrene–butadiene rubber production
workers have been studied. One was studied by the National
Institute of Occupational Safety and Health (NIOSH) in a two-plant
complex in Ohio, USA (McMichael et al., 1974, 1976; Meinhardt et
al., 1982), and the other comprised workers from eight facilities
in the USA and Canada who were studied by researchers from the
Johns Hopkins’ University (Matanoski & Schwartz, 1987;
Matanoski et al., 1990, 1993).
Subsequently, researchers from the University of Alabama at
Birmingham (Delzell et al. 1996) studied the two-plant complex
originally investigated by NIOSH plus seven of the eight plants
studied by the Johns Hopkins’ University. The Johns Hopkins’
researchers also conducted nested case–control studies within this
working population (Santos-Burgoa et al., 1992; Matanoski et al.,
1997). The University of Alabama at Birmingham group recently
updated the follow-up of the cohort and revised and refined their
assess-ment of exposures both to butadiene and to possible
confounding co-exposures (Macaluso et al., 2004). A number of
largely overlapping publications from these groups have been
reviewed. The most recent results were published by Graff et al.
(2005), Sathiakumar et al. (2005), and Cheng et al. (2007).
In addition to industry-based studies, a population-based
case–control study in Canada (Parent et al., 2000) and a cohort
study of students at a high school adjacent to a styrene–butadiene
rubber production plant in the USA (Loughlin et al., 1999) are also
reviewed here.
Overall, the available studies focused consistently on a
possible increased risk for neoplasms of the lymphatic and
haematopoietic system from exposure to butadiene.
Epidemiological studies of cancer and exposure to butadiene are
summarized in Table 18.
2.2 Industry-based studies
2.2.1 Monomer production
A cohort mortality study included men who were assigned to any
of three butadiene production units located within several chemical
plants in the Kanawha Valley of West Virginia, USA. Of the 364 men
included in the study, 277 (76%) were employed in a ‘Rubber
Reserve’ plant that operated during the Second World War (Ward et
al., 1995). The plants produced butadiene from ethanol or from
olefin cracking. The butadiene production units included in this
study were selected from an index of chemical departments that was
developed by the Union Carbide Corporation and included only
departments where butadiene was a primary product and neither
benzene nor ethylene oxide was present. The cohort studied was part
of a large cohort of 29 139 chemical workers whose mortality
experience had been reported earlier, although without regard to
specific exposures (Rinsky et al., 1988). Three subjects were lost
to follow-up (0.8%). Mortality from all cancers was not increased
(48 deaths; standardized mortality ratio [SMR], 1.1; 95% confidence
interval [CI], 0. 8–1.4). Seven deaths from lymphatic and
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Table 18. Epidemiological studies of exposure to 1,3-butadiene
and the risk for lympho-haematopoietic neoplasms
Reference, location
Cohort description
Exposure assessment
Organ site (ICD code) Exposure categories
No. of cases/ deaths
Relative risk (95% CI) Adjustment for potential confounders
Comments
Butadiene monomer production
Ward, E.H. et al. (1995, 1996), USA
364 male workers in three units
Employment in butadiene departments; no benzene or ethylene
oxide present
All (140–208) Lymphatic and haematopoietic Lymphosarcoma and
reticulosarcoma (200) Leukaemia (204–208)
48 7 4 2
SMR 1.1 (0.8–1.4) 1.8 (0.7–3.6) 5.8 (1.6–14.8) 1.2 (0.2–4.4)
Age, time period; county reference rates
All 4 cases of lympho/reticulo-sarcomas had been employed ≥ 2
years (SMR, 8.3; 95% CI, 1.6–14.8), as had those of stomach cancer
(SMR, 6.6; 95% CI, 2.1–15.3); all occurred in the rubber reserve
plant.
Divine & Hartman (2001), USA
2800 male workers employed ≥ 6 months in 1943–96
Industrial hygiene sampling data
All cancers (140–209) Lymphohaematopoietic (200–209)
Employed < 5 years 5–19 years ≥ 20 years Employed < 5
years 5–19 years ≥ 20 years High exposure < 5 years ≥ 5 years
First employed 1942–49 ≥ 1950
333 170 55 108 50 26 8 16 20 14 46 4
SMR 0.9 (0.8–1.0) 1.0 (0.8–1.1) 0.8 (0.6–1.1) 0.8 (0.7–1.0) 1.4
(1.1–1.9) 1.6 (1.0–2.3) 1.2 (0.5–2.4) 1.3 (0.8–2.2) 1.8 (1.1–2.8)
1.5 (0.8–2.5) 1.5 (1.1–2.1) 0.7 (0.2–1.8)
Age, time period, age at hire
No increasing trend by duration of employment; no increasing
trend by exposure group; lymphatic haematopoietic cancers and
lymphosarcoma significantly increased in the highest exposure
category; elevations were found in workers employed < 1950, and
were highest in short-term workers.
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Table 18 (contd)
Reference, location
Cohort description
Exposure assessment
Organ site (ICD code) Exposure categories
No. of cases/ deaths
Relative risk (95% CI) Adjustment for potential confounders
Comments
Divine & Hartman (2001) (contd)
Non-Hodgkin lymphoma (200, 202) Leukaemia (204–207)
Employed < 5 years 5–19 years ≥ 20 years High exposure < 5
years ≥ 5 years First employed 1942–49 ≥ 1950 Employed < 5 years
5–19 years ≥ 20 years High exposure < 5 years ≥ 5 years First
employed 1942–49 ≥ 1950
19 12 3 4 8 4 17 2 18 9 2 7 8 5 18 0
1.5 (0.9–2.3) 1.3 (0.3–3.7) 0.9 (0.3–2.3) 2.0 (0.9–3.9) 1.1
(0.3–2.9) 1.6 (0.9–2.6) 1.6 (0.9–2.6) 0.9 (0.1–3.2) 1.3 (0.8–2.0)
1.4 (0.6–2.6) 0.7 (0.1–2.6) 1.5 (0.6–3.1) 1.9 (0.8–3.7) 1.4
(0.4–3.2) 1.5 (0.9–2.4) 0 (0–178)
Tsai et al. (2001), USA
614 male workers
Employed ≥ 5 years in butadiene production; most 8-h TWAs for
butadiene < 10 ppm
All cancers Lymphatic and haemopoietic (200–209)
16 3
SMR 0.6 (0.3–0.9) 1.1 (0.3–1.5)
Age, race, calendar year; reference county-specific rates
A concurrent morbidity study failed to show differences in
haematological values between butadiene-exposed and unexposed
workers within the complex.
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Table 18 (contd)
Reference, location
Cohort description
Exposure assessment
Organ site (ICD code) Exposure categories
No. of cases/ deaths
Relative risk (95% CI) Adjustment for potential confounders
Comments
Styrene–butadiene rubber (SBR) production
McMichael et al. (1976), USA
Case–cohort of 6678 male rubber workers
Employment for > 2 years in SBR production based on work
histories
All lymphatic and haematopoietic (200–9) Lymphatic leukaemia
(204)
≥ 5 years in synthetic plant
51 14
6.2 (4.1–12.5)a 3.9 (2.6–8.0)a
Age No information on exposure to specific agents
Meinhardt et al. (1982), USA (overlapping with Delzell et al.,
1996)
2756 white men employed for at least 6 months (Plant A, 1662
men; Plant B, 1094 men)
Duration and time of employment
Lymphatic and haematopoietic (200–5) Lymphosarcoma and
reticulosarcoma Leukaemia (204)
Plant A Plant A, total Plant A, working 1943–45 Plant B, total
Plant A, total Plant A, working 1943–45 Plant B, total
9 3 3 1 5 5 1
SMR 1.6 1.8 2.1 1.3 2.0 2.8 1.0
Age, time period, race
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Table 18 (contd)
Reference, location
Cohort description
Exposure assessment
Organ site (ICD code) Exposure categories
No. of cases/ deaths
Relative risk (95% CI) Adjustment for potential confounders
Comments
Delzell et al. (1996), USA and Canada (includes data from
Meinhardt et al. (1982); Matanoski & Schwartz, 1987; Lemen et
al., 1990; Matanoski et al., 1990, Santos-Burgoa et al., 1992;
Matanoski et al., 1993, 1997)
15 649 workers employed for at least 1 year in eight production
plants in 1943–91
8281 unique combinations of work area/job title, grouped in 308
work areas with similar exposure
All cancers (140–208) Lymphosarcoma (200) Other lymphopoietic
(202) Leukaemia (204–208)
Five main process groups and seven sub-groups Polymerization
Maintenance Labour Laboratories
950 11 42 48 15 13 10
0.93 (0.87–0.99) 0.8 (0.4–1.4) 1.0 (0.7–1.5) 1.3 (1.0–1.7) 2.5
(1.4–4.1) 2.7 (1.4–4.5) 4.3 (2.1–7.9)
Age, race, calendar time
Among ‘ever hourly paid’ workers, 45 leukaemia deaths (SMR, 1.4;
95% CI, 1.0–1.9); SMR for hourly workers having worked for > 10
years and hired ≥ 20 years ago, 2.2 (95% CI, 1.5–3.2) based on 28
leukaemia deaths
Macaluso et al. (1996), USA and Canada (over-lapping with
Delzell et al., 1996)
12 412 subjects
Retrospective quantitative estimates of exposure to butadiene,
styrene and benzene by work area
Leukaemia (204–208) ppm–years 0 < 1 1–19 20–79 ≥ 80 p-trend 0
< 1 1–19 20–79 ≥ 80 p-trend
8 4 12 16 18
SMR 0.8 (0.3–1.5) 0.4 (0.4–1.1) 1.3 (0.7–2.3) 1.7 (1.0–2.7) 2.6
(1.6–4.1) = 0.01 Mantel-Haenszel 1.0 2.0 (NR) 2.1 (NR) 2.4 (NR) 4.5
(NR) 0.01
Age, race, co-exposure to styrene and benzene; Mantel-Haenszel
rate ratios adjusted by race, cumulative exposure to styrene
Including 7 decedents for whom leukaemia was listed as
contributory cause of death
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Table 18 (contd)
Reference, location
Cohort description
Exposure assessment
Organ site (ICD code) Exposure categories
No. of cases/ deaths
Relative risk (95% CI) Adjustment for potential confounders
Comments
Matanoski et al. (1997), USA and Canada (over-lapping with
Delzell et al., 1996)
Nested case–control study from a cohort of 12 113 employees at
SBR plant
Estimated cumulative exposure and average intensity of exposure
to butadiene
Hodgkin lymphoma (201) Leukaemia
Average intensity of exposure to butadiene, 1 ppm compared with
0 ppm
8 26
1.7 (0.99–3.0) 1.5 (1.1–2.1)
Birth year, age at hire before 1950, race, length of
employ-ment
Additional results from the same cohort are presented in the
text (Matanoski & Schwartz, 1987; Matanoski et al., 1990;
Santos-Burgoa et al., 1992); non-Hodgkin lymphoma and multiple
myeloma were not associated with exposure to butadiene.
Sathiakumar et al. (1998), USA and Canada (same as Delzell et
al., 1996)
12 412 subjects
See Macaluso et al. (1996)
Non-Hodgkin lymphoma (202)
Hourly workers ≥ 10 years worked and ≥ 20 years since hire
15
SMR 1.4 (0.8–2.3)
Age, race, calendar time
No pattern by duration of employment, time since hire, period of
hire or process group
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Table 18 (contd)
Reference, location
Cohort description
Exposure assessment
Organ site (ICD code) Exposure categories
No. of cases/ deaths
Relative risk (95% CI) Adjustment for potential confounders
Comments
Delzell et al. (2001), USA and Canada
13 130 men employed for at least 1 year during 1943–91 at 6 SBR
plants
Quantitative estimates
Leukaemia (204–208)
Butadiene ppm–years 0 > 0–< 86.3 86.3–< 362.2 ≥ 362.2
p-trend Butadiene ppm–years 0 > 0–< 86.3 86.3–< 362.2 ≥
362.2 p-trend
7 17 18 17 7 17 18 17
Poisson regression 1.0 1.2 (0.5–3.0) 2.0 (0.8–4.8) 3.8 (1.6–9.1)
< 0.001 1.0 1.3 (0.4–4.3) 1.3 (0.4–4.6) 2.3 (0.6–8.3) =
0.250
Age, years since hire Age, years since hire, co-exposure to
other agents
The association of risk for leukaemia with butadiene was
stronger for ppm–years due to exposure intensities > 100
ppm.
Butadiene ppm–years exposure intensity < 100 ppm 0 >
0–< 37.8 37.8–< 96.3 ≥ 96.3 p-trend Butadiene ppm–years
exposure intensity > 100 ppm 0 > 0–< 46.5 46.5–< 234.3
≥ 234.3 p-trend
7 17 17 18 7 17 17 18
1.0 1.1 (0.5-2.7) 2.8 (1.2-6.8) 3.0 (1.2-7.1) = 0.25 1.0 2.1
(0.9–5.1) 2.8 (1.2–6.7) 5.8 (2.4–13.8) = 0.01
Age, years since hire Age, years since hire
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Table 18 (contd)
Reference, location
Cohort description
Exposure assessment
Organ site (ICD code) Exposure categories
No. of cases/ deaths
Relative risk (95% CI) Adjustment for potential confounders
Comments
Graff et al. (2005), USA and Canada
16 579 men working at 6 plants ≥ 1 year by 1991 and followed up
through to 1998
Same as Delzell et al. (2001); cumulative exposure estimates for
butadiene, styrene and DMDTC
Leukaemia (204–208) Leukaemia (204–208)
Butadiene ppm–years 0 > 0–< 33.7 33.7–< 184.7
184.7–< 425.0 ≥ 425.0 p-trend Butadiene ppm–years 0 > 0–<
33.7 33.7–< 184.7 184.7–< 425.0 ≥ 425.0 p-trend
10 7 18 18 18 10 17 18 18 18
Poisson regression 1.0 1.4 (0.7–3.1) 1.2 (0.6–2.7) 2.9 (1.4–6.4)
3.7 (1.7–8.0) < 0.001 1.0 1.4 (0.5–3.9) 0.9 (0.3–2.6) 2.1
(0.7–6.2) 3.0 (1.0–9.2) = 0.028
Age, years since hire Age, years since hire, other agents
SMR analyses with external reference rates (national and
state-specific) also conducted and results for leukaemia consistent
with those of internal analysis using Poisson regression
models.
Chronic lymphocytic leukaemia (204.1) Chronic myelogenous
leukaemia (205.1) Other leukaemia
< 33.7 33.7–< 425.0 ≥ 425.0 p-trend < 33.7 33.7–<
425.0 ≥ 425.0 p-trend < 33.7 33.7–< 425.0 ≥ 425.0 p-trend
7 11 7 3 8 5 5 5 4
1.0 1.5 (0.6–4.0) 3.9 (1.3–11.0) = 0.014 1.0 2.7 (0.7–10.4) 7.2
(1.7–30.5) = 0.007 1.0 1.1 (0.3–3.9) 4.0 (0.3–15.0) = 0.060
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Table 18 (contd)
Reference, location
Cohort description
Exposure assessment
Organ site (ICD code) Exposure categories
No. of cases/ deaths
Relative risk (95% CI) Adjustment for potential confounders
Comments
Sathiakumar et al. (2005), USA and Canada
17 924 male workers employed ≥ 1 year before 1992 followed
through to 1998
Same as Delzell et al. (1996)
Non-Hodgkin lymphoma (200, 202) All cancer Lymphohaematopoietic
(200–208) Hodgkin lymphoma Multiple myeloma (203) Leukaemia
(204–208) Chronic lymphocytic leukaemia (204.1)
All workers Hourly workers All workers Hourly workers Hourly
workers ≥ 20 years since hire –10 years worked Production
Polymerization Coagulation Finishing Labour maintenance
Laboratories All workers Hourly workers
53 49 1608 162 12 26 71 63 19 18 10 19 15 14 16 15
SMR 1.0 (0.8–1.3) 1.1 (0.8–1.5) 0.92 (0.88–0.97) 1.06 (0.9–1.2)
1.1 (0.6–2.0) 0.95 (0.62–1.4) 1.2 (0.9–1.5) 1.2 (0.9–1.6) 2.6
(1.6–4.0) 2.0 (1.2–3.2) 2.3 (1.1–4.3) 1.6 (0.9–2.4) 2.0 (1.1–3.4)
3.3 (1.8–5.5) 1.5 (0.9–2.5) 1.7 (0.96–2.8)
Age, race, calendar period
Leukaemia excesses in production mainly due to chronic lymphatic
leukaemia: polymer-ization (8 cases; SMR, 4.97; 95% CI, 2.15–9.80),
coagulation (5 cases; SMR, 6.07; 95% CI, 1.97–14.17) and finishing
(7 cases; SMR, 3.44; 95% CI, 1.38–7.09); myelo-genous leukaemia
particularly high in maintenance labour (acute, 5 cases; SMR, 2.95;
95% CI, 0.96–6.88) and laboratory (total, 6 cases; SMR, 3.31; 95%
CI, 1.22–7.20; chronic, 3 cases; SMR, 5.22; 95% CI, 1.08–15.26)
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Table 18 (contd)
Reference, location
Cohort description
Exposure assessment
Organ site (ICD code) Exposure categories
No. of cases/ deaths
Relative risk (95% CI) Adjustment for potential confounders
Comments
Delzell et al. (2006), USA and Canada
Non-Hodgkin lymphoma (200, 202) Non-Hodgkin lymphoma and chronic
lympho- cytic leukaemia combined (200, 202, 204.1) Lymphoid
neoplasms (200–204) Myeloid neoplasms (205, 206),
(erythroleukaemia, myelofibrosis, myelosdysplasia, polycythemia
vera, myeloproliferative disease)
Butadiene ppm–years 0 > 0–< 33.7 33.7–< 184.7
184.7–< 425.0 ≥ 425.0 0 > 0–< 33.7 33.7–< 184.7
184.7–< 425.0 ≥ 425.0 0 > 0–< 33.7 33.7–< 184.7
184.7–< 425.0 ≥ 425.0 < 33.7 33.7–< 184.7 184.7–< 425.0
≥ 425.0
11 16 10 12 9 12 18 14 17 14 24 28 25 21 22 19 15 11 11
1.0 1.0 (0.4–2.6) 0.4 (0.1–1.2) 0.9 (0.3–2.7) 0.7 (0.2–2.3) 1.0
0.9 (0.4–2.1) 0.4 (0.2–1.1) 1.0 (0.4–2.7) 0.9 (0.3–2.7) 1.0 0.9
(0.5–2.0) 0.7 (0.3–1.6) 1.3 (0.6–3.1) 1.5 (0.6–3.8) 1.0 0.8
(0.3–1.7) 1.6 (0.6–4.1) 2.4 (0.9–6.8)
Age, years since hire, other agents
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Table 18 (contd)
Reference, location
Cohort description
Exposure assessment
Organ site (ICD code) Exposure categories
No. of cases/ deaths
Relative risk (95% CI) Adjustment for potential confounders
Comments
Cheng et al. (2007), USA and Canada
Same as Sathiakumar et al. (2005)
Same as Delzell et al. (2001)
Leukaemia (204–208) Cumulative ppm–years Continuous Mean scored
deciles Total number of peaks Continuous Mean scored deciles
Average intensity Continuous Mean scored deciles
81 Cox regression coefficient (ββββ) for exposure–response SE,
p-value β = 3.0*10–4 SE 1.4*10–4, p = 0.04 (0.1*10–4–5.8*10–4) β =
5.8*10-4 SE 2.7*10–4, p = 0.03 (0.5*10–4–11.1*10–4) β = 5.6*10–5 SE
2.4*10–5, p = 0.02 (0.8*10–5–10.4*10–5) β = 7.5*10–5 SE 3.7*10–5, p
= 0.04 (0.3*10–5–14.7*10–5) β = 3.6*10–3 SE 2.1*10–3, p = 0.09
(–0.5*10–3–7.7*10–3) β = 3.8*10–3 SE 3.7*10–3, p = 0.40
(–3.5*10–3–11.0*10–3)
Age, year of birth, race, plant, years since hire, DMDTC
Lymphoid neo-plasms associated with butadiene ppm–years and
myeloid neoplasms with butadiene peaks; neither trend significant
after adjusting for covariates; DMDTC as a continuous variable not
associated with leukaemia; risk estimates for quartiles of exposure
to DMDTC significantly increased without monotonic trend.
CI, confidence interval; DMDTC, dimethyldithiocarbamate; ICD,
International Classification of Diseases; NR, not reported; SE,
standard error; SMR, standardized mortality ratio; TWA,
time-weighted average a 99.9% confidence interval
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haematopoietic cancers occurred (SMR, 1.8; 95% CI, 0.7–3.6),
including four cases of lymphosarcoma and reticulosarcoma (SMR,
5.8; 95% CI, 1.6–14.8). Three cases had a duration of employment of
2 years or more (SMR, 8.3; p < 0.05). Two cases of leukaemia
(SMR, 1.2; 95% CI, 0.2–4.4) also occurred. A non-significant excess
of mortality from stomach cancer was observed (SMR, 2.4; 95% CI,
0.8–5.7). All five cases of stomach cancer occurred among the
subset of workers who had been employed in the ‘Rubber Reserve’
plant for 2 years or more (SMR, 6.6; 95% CI, 2.1–15.3).
The mortality of a cohort of workers who manufactured butadiene
monomer in Texas, USA (Downs et al., 1987), has been investigated
repeatedly with updated and extended follow-up (Divine, 1990;
Divine et al., 1993; Divine & Hartman, 1996). The latest
avail-able update, that included 5 additional years of follow-up up
to 31 December 1999, was reported by Divine and Hartman (2001). The
cohort at that time included 2800 male workers (of whom 216 were
non-white and 10 were of unknown race) who had been employed for at
least 6 months between 1943 and 1996. Exposure assessment was based
on job history and industrial hygiene sampling data for the years
after 1981. Each job was assigned a score for exposure to butadiene
that took into account calendar period and type of operation. No
information was reported on exposure to chemicals other than
butadiene. The number of workers lost to follow-up was 192 (6.7%),
all but 17 (< 1%) of whom were known to be alive at the end of
1998. A total of 1422 deaths were identified through to 1999, and
death certificates were obtained for all but 19 (1.3%) of the
deaths. SMRs were calculated using mortality rates for the US
population as the reference. The SMR for all causes of death was
0.9 (95% CI, 0.8–0.9) and that for all cancers (333 deaths) was 0.9
(95% CI, 0.8–1.0). Fifty deaths from lymphatic and haematopoietic
cancers (International Classification of Diseases [ICD]-8, 200–209;
SMR, 1.4; 95% CI, 1.1–1.9), nine deaths from lymphosarcoma and
reticulosarcoma (ICD-8, 200; SMR, 2.0; 95% CI, 0.9–3.9), 19 deaths
from non-Hodgkin lymphoma (ICD-8, 200, 202; SMR, 1.5; 95% CI,
0.9–2.3), four deaths from Hodgkin lymphoma (ICD-8, 201; SMR, 1.6;
95% CI, 0.4–4.1), 18 deaths from leukaemia (ICD-8, 204–207; SMR,
1.3; 95% CI, 0.8–2.0), seven deaths from mul-tiple myeloma (ICD-8,
203; SMR, 1.3; 95% CI, 0.5–2.6) and 18 deaths from cancer of other
lymphatic tissue (ICD-8, 202, 203, 208; SMR, 1.3; 95% CI, 0.8–2.1)
were observed. However, the latter category overlapped with
non-Hodgkin lymphoma and multiple myeloma. The SMRs for the
lymphatic and haematopoietic cancers did not increase with length
of employment. Analysis by date of employment showed an increased
risk for lymphatic and haematopoietic cancers among those first
employed between 1942 and 1949. A separate mortality analysis for
non-whites showed lower than expected mortality for all malignant
neoplasms (17 observed, 19 expected) and a single death from
lymphatic and haematopoietic cancer. Subcohort analyses were made
for groups that were classified as having background, low and
varied exposure. The background-exposure group in-cluded persons in
offices, transportation, utilities and warehouses; the low-exposure
group had spent some time in operating units; and the
varied-exposure group included those with greatest potential
exposure in operating units, laboratories and maintenance. In the
background-exposure group, four deaths from lymphatic and
haematopoietic cancers
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1,3-BUTADIENE 81
(ICD-8, 200–209) were observed among those employed for < 5
years (SMR, 1.9; 95% CI, 0.5–4.7) and four among those exposed for
> 5 years (SMR, 1.7; 95% CI, 0.5–4.3). Eleven deaths from
lymphatic and haematopoietic cancers (ICD-8, 200–209) were observed
in the low-exposure group, seven of which were among those with
< 5 years of employment (SMR, 0.9; 95% CI, 0.4–1.9) and four
among those employed for > 5 years (SMR, 0.6; 95% CI, 0.2–1.6).
In the varied-exposure group, with the highest potential for
exposure to butadiene, 34 deaths from lymphatic and haematopoietic
cancers (ICD-8, 200–209) were observed, 20 of which were among
those employed for < 5 years (SMR, 1.8; 95% CI, 1.1–2.8) and 14
among those exposed for > 5 years (SMR, 1.5; 95% CI, 0.8–2.5).
In all groups, the SMRs for lymphatic and haematopoietic cancer
decreased with duration of employment. For lymphosarcoma and
reticulosarcoma, two deaths occurred in the low-exposure group (one
among those employed < 5 years and one among those employed >
5 years) and seven deaths were observed in the varied-exposure
group, five of which were among those employed for < 5 years
(SMR, 3.7; 95% CI, 1.2–8.7) and two among those employed for > 5
years (SMR, 1.87; 95% CI, 0.23–6.76). Three deaths from leukaemia
occurred (SMR, 0.7; 95% CI, 0.1–2.0) in the low-exposure subgroup
and 13 cases were observed in the varied-exposure group, eight of
which were among those employed for < 5 years (SMR, 1.9; 95% CI,
0.8–3.7) and five among those employed > 5 years (SMR, 1.4; 95%
CI, 0.4–3.2). Six deaths from non-Hodgkin lymphoma were observed in
the low-exposure group, four among short-term employees (SMR, 1.5;
95% CI, 0.4–3.8) and two among those employed for > 5 years
(SMR, 0.9; 95% CI, 0.1–3.2), and 12 deaths occurred in the
varied-exposure group, eight of which were among those employed for
< 5 years (SMR, 2.0; 95% CI, 0.9–3.9) and four among long-term
employees (SMR, 1.1; 95% CI, 0.3–2.9). The ‘varied-exposure’ group
with high potential for exposure to butadiene showed elevated SMR
estimates for all subcategories of lymphatic and haematopoietic
cancers, but the increase was statistically significant only for
lympho/reticulosarcoma among those employed for < 5 years.
Slightly elevated SMRs were also found in the low-exposure group
for cancer of the kidney (three cases; SMR, 1.6; 95% CI, 0.3–4.6;
and three cases; SMR, 1.9; 95% CI, 0.4–5.4; among short- and
long-term employees, respectively). In the varied-exposure group, a
suggestive excess incidence of kidney cancer was only present among
those employed for > 5 years (four cases; SMR, 1.65; 95% CI,
0.45–4.22). Survival analysis by Cox regression was carried out
using a cumulative exposure score as a time-dependent explanatory
variable for all lymphohaematopoietic neoplasms, non-Hodgkin
lymphoma and leukaemia. None of these cancers was significantly
associated with the cumulative exposure score. The elevated risk
for all the lymphohaematopoietic cancers and their subcategories
occurred among persons who were first employed before 1950. [The
Working Group noted that although there was no evidence of an
exposure–response relationship, it is probable that many workers
during the years of the Second World War would have had short but
relatively intense exposures, and thus duration of exposure may not
be the most relevant dose metric.]
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Another relatively small retrospective mortality study, together
with a prospective morbidity survey, was performed on male
employees at the Shell Deer Park Manufacturing Complex in the USA
(Cowles et al., 1994) and was updated with a 9-year extension of
the follow-up (Tsai et al., 2001). Butadiene monomer production
took place in the facility between 1941 and 1948 and from 1970
onwards. The cohort comprised 614 eligible male employees who had
worked for 5 years or more in jobs that entailed potential exposure
to butadiene. Also eligible were employees who had worked for at
least half of their total duration of employment during 1948–89 in
a job that entailed potential exposure to butadiene (with a minimum
3-month period in such jobs). Female employees were excluded
because of the small number (35) who met the eligibility criteria.
Industrial hygiene data from 1979 to 1992 showed that few exposures
to buta-diene exceeded 10 ppm [22 mg/m3] as an 8-h TWA and that
most were below 1 ppm [2.2 mg/m3]; the arithmetic mean exposure was
3.5 ppm [7.7 mg/m3]. Only one study member had unknown vital status
at the end of the follow-up. Person–years were accrued after 1
April 1948 from the time that a person first met the eligibility
criteria. Death certificates were obtained for all known decedents.
SMRs adjusted for age, race and calendar year were calculated using
county-specific mortality rates as the reference. Six hundred and
fourteen cohort members contributed a total of 12 391 person–years
during the expanded study period, during which 61 deaths were
identified. The SMR for all causes of death was 0.55 (95% CI,
0.42–0.70) and that for all malignant neoplasms was 0.6 (16 deaths;
95% CI, 0.3–0.9). Eight deaths were due to lung cancer (SMR, 0.7;
95% CI, 0.2–3.1) and three to cancer of the lymphatic and
haematopoietic tissues (SMR, 1.1; 95% CI, 0.3–1.5). No deaths from
leukaemia were observed, whereas one death was expected. The
morbidity study included 289 of the 614 cohort members who were
actively employed at some time between 1 January 1992 and 31
December 1998. The morbidity experience of this group was compared
with that of an internal comparison group of 1386 active employees
during the same period who had had no exposure to butadiene. A
morbidity event was defined as an absence from work of > 5 days
during 1992–98 that resulted from a specific diagnosed disorder. No
meaningful differences in morbidity events between the
butadiene-exposed and unexposed employees in the rest of the Shell
Deer Park Manu-facturing Complex were observed. [The Working Group
noted that one criteria for in-clusion in the cohort (at least half
of total employment during 1948–89 in a potentially exposed job)
was a potential source of bias, and that the SMR for all causes was
un-usually low.]
2.2.2 Styrene–butadiene rubber production
The 9-year mortality experience of a cohort of 6678 male rubber
workers from a single, large tyre manufacturing plant in Ohio, USA,
approximately 4% of whom worked in the manufacture of synthetic
rubber, was investigated during 1964–72 (McMichael et al., 1974,
1976). Death rates from various specific causes were increased and
included lymphatic and haematopoietic cancers in general (43
observed deaths; SMR, 1.36),
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lymphosarcoma and Hodgkin lymphoma (15 observed; SMR, 1.64) and
leukaemia (17 observed; SMR, 1.26). A case–cohort study was nested
within the cohort to investigate the association of excesses of
mortality with specific jobs within the rubber industry to compare
workers who died from cancers in the 10-year period 1964–73 with a
sample of members of the whole cohort and to elucidate differences
in work histories (McMichael et al., 1976). A 6.2-fold increase in
risk for lymphatic and haematopoietic cancers (99.9% CI, 4.1–12.5)
and a 3.9-fold increase in risk for lymphatic leukaemia (99.9% CI,
2.6–8.0) were found in association with more than 5 years of work
in manufacturing units that produced mainly styrene–butadiene
rubber during 1940–60. [The Working Group noted that no information
was provided on exposure to specific substances including
potentially confounding chemicals such as benzene.]
Meinhardt et al. (1982) studied the mortality experience of
white male workers who had been employed for at least 6 months in a
two-plant complex styrene–butadiene rubber facility in the USA. A
total of 1662 workers employed in Plant A between 1943 and 1976 and
1094 workers employed in Plant B between 1950 and 1976 were
followed up through to 31 March 1976. Nine deaths from cancer of
the lymphatic and haematopoietic tissues (ICD-7, 200–205) were seen
in workers in Plant A (SMR, 1.6). The SMR among those from Plant A
who were first employed between January 1943 and December 1945 was
2.1. Five deaths from leukaemia (ICD-7, 204) were observed in Plant
A among workers employed between 1943 and 1945 (SMR, 2.8). In Plant
B, two deaths from lymphatic and haematopoietic neoplasms (one
lymphosarcoma/reticulosarcoma and one leukaemia) were observed.
Matanoski et al. (1990) investigated mortality patterns from
1943 (synthetic rubber production began in 1942) through to 1982
among 12 113 employees at styrene–buta-diene rubber plants in
Canada and the USA who had previously been followed up through to
1979 by Matanoski and Schwartz (1987). Overall, there were no
increases in mortality from lymphatic and haematopoietic cancers.
When employees were classified according to their longest-held job,
production workers (presumed by the authors to be those with
highest exposures to butadiene) had a significant excess of ‘other
lymphatic cancer’ (nine deaths; SMR, 2.60; 95% CI, 1.19–4.94). When
mortality among production workers was examined by race, a
significant excess for leukaemia was seen in blacks (three deaths;
SMR, 6.56; 95% CI, 1.35–19.06). Of 92 deaths among black production
workers, six were from all lymphohaemopoietic cancers (SMR, 5.07;
95% CI, 1.87–11.07).
Nested case–control studies were conducted within the
styrene–butadiene rubber cohort in the USA and Canada
(Santos-Burgoa et al., 1992; Matanoski et al., 1997). In the study
by Santos-Burgoa et al. (1992), 59 cases of lymphatic and
haematopoietic cancer in male workers (1943–82) were matched to 193
controls by plant, age, year of hire, duration of employment and
survival to time of death of the case. Each job was assigned an
estimated rank of exposure to butadiene and styrene, and cumulated
exposure for each worker was calculated using employment histories.
A strong association was identified for both butadiene (odds ratio,
9.4; 95% CI, 2.1–22.9) and styrene (odds ratio, 3.1; 95% CI,
0.8–11.2). After controlling for the other exposure, the odds ratio
for
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84 IARC MONOGRAPHS VOLUME 97
exposure to butadiene remained high and significant (odds ratio,
7.4; 95% CI, 1.3–41.3) whereas the relative risk estimate for
styrene was approximately unity (odds ratio, 1.1; 95% CI,
0.23–4.95).
Matanoski et al. (1997) conducted a second case–control study
that was nested in the styrene–butadiene cohort and included as
cases most of the same lymphatic and haemato-poietic cancer
decedents studied by Santos-Burgoa et al. (1992). In this study,
hospital records obtained for 55 of the 59 cases studied by
Santos-Burgoa et al. (1992) were re-viewed to confirm death
certificate reports of lymphatic and haematopoietic cancer. The
review confirmed all leukaemias, eliminated two cases and added one
case of non-Hodgkin lymphoma and confirmed all cases of Hodgkin
lymphoma and multiple myeloma. The final case groups included 58
total lymphatic and haematopoietic cancers, 12 non-Hodgkin
lymphomas (seven lymphosarcomas and five other non-Hodgkin
lymphomas), eight Hodgkin lymphomas, 26 leukaemias and 10 multiple
myelomas. Controls were 1242 employees who were chosen to reflect
the distribution of the cohort by plant and age, who had to have
lived at least as long as cases and who represented approximately
1% of the cohort, but were not matched individually to cases.
Quantitative exposure estimates for butadiene and styrene were
developed by using exposure measurements for work areas and jobs,
when available, and a modelling procedure to obtain estimates for
jobs that had no measurements. Plant- and work area-specific
exposure estimates were linked to work histories to obtain indices
of cumulative exposure (ppm–months) and average intensity of
exposure (ppm). Odds ratios for an average intensity of exposure of
1 ppm compared with 0 ppm and for ppm–months as a con-tinuous
variable were estimated using logarithmically transformed exposure
data in unconditional logistic regression models that controlled
for year of birth, period of hire, age at hire, race and length of
employment. Leukaemia and Hodgkin lymphoma were associated
positively